Acyclic 1,4-Stereocontrol via the Allylic Diazene Rearrangement: Development, Applications, and the Essential Role of Kinetic E Stereoselectivity in Tosylhydrazone Formation

Abstract

We report full details of a method for 1,3-reductive transposition of α-alkoxy-α,β-unsaturated hydrazones to provide E-alkenes with high 1,4-stereocontrol between the two respective allylic stereocenters. The process couples a chelation-controlled reduction of the hydrazone with an in situ allylic strain controlled retro-ene reaction of an allyl diazene, i.e., an allylic diazene rearrangement. Such stereotriads are frequently observed motifs in natural products. We observed a fortuitous kinetic preference for the E-hydrazone geometry during the hydrazonation reaction, as only the E-isomers could undergo chelation-controlled reduction.

An Update of N-Tosylhydrazones: Versatile Reagents for Metal-Catalyzed and Metal-Free Coupling Reactions

“…136 In 2017, McIntosh and co-workers utilized catecholborane (HBCat) in the 1,3-reductive transposition of N-tosylhydrazones derived from α-chiral α-alkoxy enones to afford highly 1,4-stereoselective (E)-alkenes (Scheme 68). 137 The procedure involved an acid-mediated hydrazone reduction via the chelation transition state T78, and then an allylic diazene rearrangement via T79.…”

Concise Access to the Skeleton of Protoilludane Sesquiterpenes through a Photochemical Reaction Cascade: Total Synthesis of Atlanticone C

“…Instead, the ketone was converted into hydrazone 9 by condensation [23] with N-tosylhydrazine (58 %yield, 36 %o fu nreacted starting material). Subsequent reduction according to the method of Kabalka et al [24] not only delivered the hydride from the correct diastereotopic face via intermediate 10 but also established the double bond in product 11 at the desired position C-9/C-10.In order to adjust the oxidation state at positions C-6, C-7, and C-8, the 1,3-dioxane ring of intermediate 11 had to be opened. Reported procedures for the ring opening of methylene acetals [25] require acidic conditions,w hich turned out to be not perfectly compatible with the substrate.F or example,t he yield of deprotection with trifluoroacetic acid anhydride and acetic acid in CH 2 Cl 2 [26] was only 36 %.…”

“…Instead, the ketone was converted into hydrazone 9 by condensation [23] with N-tosylhydrazine (58 %yield, 36 %o fu nreacted starting material). Subsequent reduction according to the method of Kabalka et al [24] not only delivered the hydride from the correct diastereotopic face via intermediate 10 but also established the double bond in product 11 at the desired position C-9/C-10.…”

Concise Access to the Skeleton of Protoilludane Sesquiterpenes through a Photochemical Reaction Cascade: Total Synthesis of Atlanticone C

“…In order to avoid undesirable consecutive reactions of enone 7 an Fe 2 (SO 4 ) 3 solution (c = 300 mg L À1 )i n0 .01m aqueous HCl [19] was employed to filter the desired wavelength region from fluorescent lamps emitting at am aximum of l = 350 nm. Subsequent reduction according to the method of Kabalka et al [24] not only delivered the hydride from the correct diastereotopic face via intermediate 10 but also established the double bond in product 11 at the desired position C-9/C-10. [21] Thet ransformation of ketone 7 to atlanticone C( 1) required the adjustment of the oxidation state at several carbon atoms and the introduction of the stereogenic center at carbon atom C-2.…”